Lipophilic statins linked to lower Parkinson’s risk in women: Study

Women using a specific type of blood cholesterol-lowering medication, called lipophilic statins, for at least five years may have a lower risk of developing Parkinson’s disease, according to data from more than 70,000 women followed for 15 years in France.

The results showed a dose-dependent effect, with lower Parkinson’s incidence seen in women using higher doses of lipophilic statins such as atorvastatin (sold as Lipitor and other generic names) and simvastatin (sold as Zocor, with generics available).

No such associations were observed for other types of statins.

“Given the need for neuroprotective agents in PD [Parkinson’s disease], further clinical trials are needed to examine [statins’] benefit in PD with special reference to the timing of treatment, molecule, and dose,” researchers wrote.

The study, “Statin Use and Incidence of Parkinson’s Disease in Women from the French E3N Cohort Study,” was published in the journal Movement Disorders.

Statins prescribed to lower blood cholesterol and cardiovascular disease risk

Currently available Parkinson’s treatments are only partially effective, since they are unable to markedly delay disease progression. In light of this, there is growing interest in repurposing existing medications, with established safety, for the treatment of Parkinson’s.

Statins, a class of medication widely prescribed to lower blood cholesterol levels and reduce the risk of cardiovascular disease, “represent potential candidates,” the researchers wrote.

Preclinical studies have demonstrated that statins can reduce inflammation and oxidative stress, a type of cellular damage — both of which are implicated in Parkinson’s. In addition, some studies have reported that statin use is linked to a lower incidence of Parkinson’s, while others have reported the opposite or no association at all.

Longer studies, accounting for both exposure changes and type of statins based on its ability to reach the brain, may help determine the true link between statin use and Parkinson’s risk.

With this in mind, a team led by researchers at the Université Paris-Saclay, in France, assessed the potential of statins to reduce Parkinson’s incidence by analyzing 15-year data from the large E3N study (NCT03285230).

Launched in 1990, the study enrolled 98,995 women, born between 1925 and 1950. Participants completed a self-administered questionnaire on lifestyle and medical history at the study’s start and every two to three years thereafter.

The researchers analyzed medication claims databases to assess the prescription of statins from 2004 (baseline) to 2018. Those who began statin use on July 1, 2004, or thereafter were then assessed for the development of Parkinson’s, starting five years after statin exposure.

Follow-up ended on the day of Parkinson’s diagnosis or death, or by the end of the study in December 2018.

Lipophilic statin use was associated with decreased [Parkinson’s] incidence in 73,925 French women followed for 15 years, with a dose-response relation.

Out of the 73,925 women (mean age 62.5 years) included in the study at baseline, 18,759 (25.4%) started using statins. Women on statins were generally older at baseline, had less formal education, were less physically active, and were more often current smokers and postmenopausal, among other factors.

During the 15-year follow-up, 693 women developed Parkinson’s, while 13,784 did not (used as controls).

The mean annual number of medical appointments increased similarly in both groups up to five years prior to diagnosis. After that, however, the number of consultations continued to increase in women subsequently diagnosed with Parkinson’s, while it plateaued in controls.

The annual prescription of two or more statins was significantly lower for women who were later diagnosed with Parkinson’s when compared with controls, but group differences disappeared in the five years prior the diagnosis.

A total of 524 women developed Parkinson’s at least five years after starting on statins. They were generally older, less often obese or smokers, more frequently postmenopausal, and had a more frequent history of high levels of the low-density lipoprotein, or “bad” cholesterol.

When considering these cases and adjusting for potential influencing factors, the researchers found that women who used any statin had a lower chance of developing Parkinson’s than those who were never treated with such medications. However, this difference failed to reach statistical significance.

The researchers then assessed Parkinson’s incidence according to the type of statins prescribed: lipophilic versus hydrophilic. This classification is based on their ability to dissolve in fat (lipophilic) or water (hydrophilic), meaning that lipophilic statins penetrate cells more easily and cross the blood-brain barrier more freely than hydrophilic statins.

During follow-up, 11,552 (15.6%) women used lipophilic statins and 11,198 (15.1%) used hydrophilic statins. A total of 3,991 (5.4%) used both types. Lipophilic statin users were older at baseline, more often diabetic, and had high blood pressure compared with hydrophilic statin users.

Women on lipophilic statins showed 30% lower risk of Parkinson’s diagnosis

After adjusting for potential influencing factors, the researchers found women treated with lipophilic statins showed a 30% significantly lower likelihood of being diagnosed with Parkinson’s compared with those who never used this type of statin. Higher doses of lipophilic statins were significantly associated with a lower Parkinson’s incidence.

No significant associations were seen between hydrophilic statin use and Parkinson’s development.

Among lipophilic statins, atorvastatin was the most frequently used (9.3%), followed by simvastatin (6.5%) and fluvastatin (1.8%; sold as Lescol, other generic names).

The strongest associations were seen for simvastatin, which was linked to a 41% significantly lower risk of Parkinson’s, and atorvastatin, which was associated with a 33% lower risk — although this was not statistically significant.

Overall, these findings highlighted that “lipophilic statin use was associated with decreased PD incidence in 73,925 French women followed for 15 years, with a dose-response relation,” the researchers wrote.

“Additional larger clinical trials are needed to examine issues related to the timing and duration of treatment and risk stratification,” they concluded.